title: The THO ribonucleoprotein complex is required for stem cell homeostasis in the adult mouse small intestine.
abstract: RNA processing and transport are mediated by cotranscriptionally assembled ribonucleoprotein (RNP) complexes. RNPs have been postulated to help specify coordinated gene expression, but the requirements for specific RNP complexes in mammalian development and tissue homeostasis have not been extensively evaluated. THO is an evolutionarily conserved RNP complex that links transcription with nuclear export. THO is not essential for Saccharomyces cerevisiae viability, but it is essential for early mouse embryonic development. Embryonic lethality has limited the characterization of THO requirements in adult tissues. To overcome this limitation, a mouse model has been generated that allows widespread inducible deletion of Thoc1, which encodes an essential protein subunit of THO. Widespread Thoc1 deletion disrupts homeostasis within the small intestine but does not have detectable effects in other epithelial tissues such as the related mucosa of the large intestine. Thoc1 loss compromises the proliferation and lineage-generating capacity of small intestinal stem cells, disrupting the supply of differentiated cells in this rapidly renewing tissue. These findings demonstrate that the effects of THO deficiency in the adult mouse are tissue and cell type dependent.
authors.affiliation: Department of Pharmacology & Therapeutics, Roswell Park Cancer Institute, Buffalo, New York, USA.
authors.forename: Laura
authors.initials: L
authors.lastname: Pitzonka
authors.forename: Xiaoling
authors.initials: X
authors.lastname: Wang
authors.forename: Sumana
authors.initials: S
authors.lastname: Ullas
authors.forename: David W
authors.initials: DW
authors.lastname: Wolff
authors.forename: Yanqing
authors.initials: Y
authors.lastname: Wang
authors.forename: David W
authors.initials: DW
authors.lastname: Goodrich
mesh_terms: D000818:Animals; D049109:Cell Proliferation; D002470:Cell Survival; D004268:DNA-Binding Proteins / Q000235:genetics* / Q000378:metabolism; D005260:Female; D017353:Gene Deletion; D007421:Intestine, Small / Q000166:cytology* / Q000378:metabolism / Q000648:ultrastructure; D007774:Lactation; D008321:Mammary Glands, Animal / Q000502:physiology / Q000648:ultrastructure; D051379:Mice; D008810:Mice, Inbred C57BL; D016601:RNA-Binding Proteins / Q000235:genetics* / Q000378:metabolism; D013234:Stem Cells / Q000166:cytology* / Q000378:metabolism
chemical_list: D004268:DNA-Binding Proteins; D016601:RNA-Binding Proteins; C511176:Thoc1 protein, mouse